Temperature-sensitive (Ts) mutants of simian virus 40 (SV40), an oncogenic animal virus, are being isolated and characterized. Antigenic phenotypes and complementation groups of these mutants are being determined. One mutant group has a mutant protein that acts as a regulatory molecule during acute infections as well as in SV40 transformed cells. Another group has a defective cytoplasmic-nuclear transport of the virion core protein, an abnormal accumulation of this protein in the nucleolus, and an inhibited synthesis of the major coat protein. Ts mutants are being used to characterize the virus-directed and cell-directed functions that interact during acute SV40 infections and in SV40 transformed cells. Wild type and Ts mutant viruses are used for infecting and transforming productive monkey cells, semiproductive human cells, and abortive mouse cells. Emphasis is placed on the regulatory role(s) of the cellular cyclic AMP and cyclic GMP systems during the three types of acute infections and in transformed cells.